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41.
Udaya DeSilva Laura Elnitski Jacquelyn R Idol Johannah L Doyle Weiniu Gan James W Thomas Scott Schwartz Nicole L Dietrich Stephen M Beckstrom-Sternberg Jennifer C McDowell Robert W Blakesley Gerard G Bouffard Pamela J Thomas Jeffrey W Touchman Webb Miller Eric D Green 《Genome research》2002,12(1):3-15
Williams syndrome is a complex developmental disorder that results from the heterozygous deletion of a approximately 1.6-Mb segment of human chromosome 7q11.23. These deletions are mediated by large (approximately 300 kb) duplicated blocks of DNA of near-identical sequence. Previously, we showed that the orthologous region of the mouse genome is devoid of such duplicated segments. Here, we extend our studies to include the generation of approximately 3.3 Mb of genomic sequence from the mouse Williams syndrome region, of which just over 1.4 Mb is finished to high accuracy. Comparative analyses of the mouse and human sequences within and immediately flanking the interval commonly deleted in Williams syndrome have facilitated the identification of nine previously unreported genes, provided detailed sequence-based information regarding 30 genes residing in the region, and revealed a number of potentially interesting conserved noncoding sequences. Finally, to facilitate comparative sequence analysis, we implemented several enhancements to the program, including the addition of links from annotated features within a generated percent-identity plot to specific records in public databases. Taken together, the results reported here provide an important comparative sequence resource that should catalyze additional studies of Williams syndrome, including those that aim to characterize genes within the commonly deleted interval and to develop mouse models of the disorder. 相似文献
42.
Krushkal J; Xiong M; Ferrell R; Sing CF; Turner ST; Boerwinkle E 《Human molecular genetics》1998,7(9):1379-1383
Elevated blood pressure is an important risk factor for renal-, cerebro-
and cardiovascular diseases. We used an efficient discordant sib-pair
ascertainment scheme to investigate the impact of the distal end of the
long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing
genes for the alpha1B and beta2 adrenergic receptors and the dopamine
receptor type 1A on variation of systolic blood pressure in young
Caucasians. We measured eight highly polymorphic markers spanning this
positional candidate gene-rich region in 427 individuals from 55
three-generation pedigrees containing 69 discordant sibling pairs, and
calculated multipoint identity by descent (MIBD) probabilities. The results
of genetic linkage and association tests indicate that the region between
markers D5S2093 and D5S462 is significantly linked to one or more
polymorphic genes influencing interindividual variation in systolic blood
pressure levels. Since the alpha1B adrenergic receptor and dopamine
receptor type 1A genes are located close to these markers, these data
suggest that genetic variation in one or both of these G protein-coupled
receptors, which participate in the control of vascular tone, plays an
important role in influencing interindividual variation in systolic blood
pressure levels.
相似文献
43.
44.
Human and Murine Immune Responses to a Novel Leishmania major Recombinant Protein Encoded by Members of a Multicopy Gene Family 总被引:1,自引:0,他引:1 下载免费PDF全文
John R. Webb Antonio Campos-Neto Pamela J. Ovendale Tricia I. Martin Erika J. Stromberg Roberto Badaro Steven G. Reed 《Infection and immunity》1998,66(7):3279-3289
Vaccination of BALB/c mice with Leishmania major promastigote culture filtrate proteins plus Corynebacterium parvum confers resistance to infection with L. major. To define immunogenic components of this protein mixture, we used sera from vaccinated mice to screen an L. major amastigote cDNA expression library. One of the immunoreactive clones thus obtained encoded a novel protein of L. major with a molecular mass of 22.1 kDa. The predicted amino acid sequence of this clone exhibited significant homology to eukaryotic thiol-specific-antioxidant (TSA) proteins. Therefore, we have designated this protein L. major TSA protein. Southern blot hybridization analyses indicate that there are multiple copies of the TSA gene in all species of Leishmania analyzed. Northern blot analyses demonstrated that the TSA gene is constitutively expressed in L. major promastigotes and amastigotes. Recombinant TSA protein containing an amino-terminal six-histidine tag was expressed in Escherichia coli with the pET17b system and was purified to homogeneity by affinity chromatography. Immunization of BALB/c mice with recombinant TSA protein resulted in the development of strong cellular immune responses and conferred protective immune responses against infection with L. major when the protein was combined with interleukin 12. In addition, recombinant TSA protein elicited in vitro proliferative responses from peripheral blood mononuclear cells of human leishmaniasis patients and significant TSA protein-specific antibody titers were detected in sera of both cutaneous-leishmaniasis and visceral-leishmaniasis patients. Together, these data suggest that the TSA protein may be useful as a component of a subunit vaccine against leishmaniasis. 相似文献
45.
Brain lysosomal glycosidase activity in immunosuppressed mice infected with avirulent Semliki forest virus. 下载免费PDF全文
Mice infected with an avirulent strain of Semliki forest virus show an increase in the activity of some of the brain lysosomal glycosidases. The increase in activity of these enzymes has been correlated with the histological, virological, and serological changes that result from the infection in the presence and absence of immunosuppression. Semliki forest virus alone caused the development of a mild encephalitis with perivascular infiltration, microgliosis, astrocyte hypertrophy, and a focal spongiform encephalopathy, together with an increased activity of brain N-acetyl-beta-D-glucosaminidase and beta-glucuronidase. Antilymphocyte serum given after infection marginally affected the course of the disease. Cyclophosphamide markedly delayed the development of the spongy changes in the increase in enzyme activities, but not the perivascular infiltration. It is suggested that the increased activity of the lysosomal glycosidases studied may be linked both to the development of a successful immune response and to the focal spongiform changes produced by the infection. 相似文献
46.
There are no satisfactory animal models for the study of anaerobic lung abscess. Aspiration of food, gastric mucin, or hydrochloric acid, or any combination of these, along with oropharyngeal bacteria, is commonly believed to cause aspiration pneumonia and lung abscess. In the animal model described, none of the adjuvants was effective in producing anaerobic lung abscesses. Anaerobic bacteria derived from dental scrapings of a healthy adult (Peptococcus morbillorum, Fusobacterium nucleatum, Eubacterium lentum, and Bacteroides fragilis), when inoculated transtracheally without any adjuvants into New Zealand male white rabbits, consistently produced lung abscesses. Neither B fragilis by itself nor a mixture of P. morbillorum, F. nucleatum, and E. lentum without the addition of B. fragilis produced lung abscesses. The bacterial isolates used in this study were stored in prereduced chopped-meat-glucose medium and subcultured several times and were found effective in reproducing anaerobic lung abscesses repeatedly. This animal model is suitable for the study of pathogenesis, diagnosis, and treatment of B. fragilis-associated anaerobic lung abscess. 相似文献
47.
Schwartz S Kent WJ Smit A Zhang Z Baertsch R Hardison RC Haussler D Miller W 《Genome research》2003,13(1):103-107
The Mouse Genome Analysis Consortium aligned the human and mouse genome sequences for a variety of purposes, using alignment programs that suited the various needs. For investigating issues regarding genome evolution, a particularly sensitive method was needed to permit alignment of a large proportion of the neutrally evolving regions. We selected a program called BLASTZ, an independent implementation of the Gapped BLAST algorithm specifically designed for aligning two long genomic sequences. BLASTZ was subsequently modified, both to attain efficiency adequate for aligning entire mammalian genomes and to increase its sensitivity. This work describes BLASTZ, its modifications, the hardware environment on which we run it, and several empirical studies to validate its results. 相似文献
48.
Emily Stephenson Simone Webb Prof. Muzlifah Haniffa 《European journal of immunology》2021,51(4):764-772
The development of the human immune system during embryonic and fetal life has historically been difficult to research due to limited access to human tissue. Experimental animal models have been widely used to study development but cellular and molecular programmes may not be conserved across species. The advent of multiomic single-cell technologies and an increase in human developmental tissue biobank resources have facilitated single-cell multiomic studies focused on human immune development. A critical question in the near future is "How do we best reconcile scientific findings across multiple omic modalities, developmental time, and organismic space?" In this review, we discuss the application of single-cell multiomic technologies to unravel the major cellular lineages in the prenatal human immune system. We also identify key areas where the combined power of multiomics technologies can be leveraged to address specific immunological gaps in our current knowledge and explore new research horizons in human development. 相似文献
49.
Gatzoulis MA Freeman MA Siu SC Webb GD Harris L 《The New England journal of medicine》1999,340(11):839-846
BACKGROUND: Atrial flutter and atrial fibrillation are causes of morbidity in adults with an atrial septal defect. In this study, we attempted to identify risk factors for atrial flutter and fibrillation both before and after the surgical closure of an atrial septal defect. METHODS: We searched for preoperative and postoperative atrial flutter or fibrillation in 213 adult patients (82 men and 131 women) who underwent surgical closure of atrial septal defects because of symptoms, a substantial left-to-right shunt (ratio of pulmonary to systemic blood flow, >1.5:1), or both at Toronto Hospital between 1986 and 1997. RESULTS: Forty patients (19 percent) had sustained atrial flutter or fibrillation before surgery. As compared with the patients who did not have atrial flutter or fibrillation before surgery, those who did were older (59+/-11 vs. 37+/-13 years, P<0.001) and had higher mean pulmonary arterial pressures (25.0+/-9.7 vs. 19.7+/-8.2 mm Hg, P=0.001). There were no perioperative deaths. After a mean follow-up period of 3.8+/-2.5 years, 24 of the 40 patients (60 percent) continued to have atrial flutter or fibrillation. The mean age of these patients was greater than that of the 16 who converted to sinus rhythm (P=0.02). New-onset atrial flutter or atrial fibrillation was more likely to have developed at follow-up in patients who were older than 40 years at the time of surgery than in those who were 40 or younger (5 of 67 vs. 0 of 106, P=0.008). Late events (those occurring more than one month after surgery) included stroke in six patients (all but one with atrial flutter or fibrillation, one of whom died) and death from noncardiac causes in two patients. Multivariate analysis showed that older age (>40 years) at the time of surgery (P=0.001), the presence of preoperative atrial flutter or fibrillation (P<0.001), and the presence of postoperative atrial flutter or fibrillation or junctional rhythm (P=0.02) were predictive of late postoperative atrial flutter or fibrillation. CONCLUSIONS: The risk of atrial flutter or atrial fibrillation in adults with atrial septal defects is related to the age at the time of surgical repair and the pulmonary arterial pressure. To reduce the morbidity associated with atrial flutter and fibrillation, the timely closure of atrial septal defects is warranted. 相似文献
50.
Concurrent de novo interstitial deletion of band 2p22 and reciprocal translocation (3;7)(p21;q22). 总被引:3,自引:1,他引:3 下载免费PDF全文
A child is described with a de novo interstitial deletion of band 2p22 and a reciprocal translocation (3;7)(p21;q22). The child has mild developmental delay, coloboma of the right eye, and Hirschsprung's disease. The clinical and cytogenetic findings are described. 相似文献